Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing.

Manske, M; Miotto, O; Campino, SORCID logo; Auburn, S; Almagro-Garcia, J; Maslen, G; O'Brien, J; Djimde, A; Doumbo, O; Zongo, I; +46 more...Ouedraogo, J; Michon, P; Mueller, I; Siba, P; Nzila, A; Borrmann, S; Kiara, SM; Marsh, K; Jiang, H; Su, X; Amaratunga, C; Fairhurst, R; Socheat, D; Nosten, F; Imwong, M; White, NJ; Sanders, M; Anastasi, E; Alcock, D; Drury, E; Oyola, S; Quail, MA; Turner, DJ; Ruano-Rubio, V; Jyothi, D; Amenga-Etego, L; Hubbart, C; Jeffreys, A; Rowlands, K; Sutherland, CORCID logo; Roper, CORCID logo; Mangano, V; Modiano, D; Tan, JC; Ferdig, MT; Amambua-Ngwa, AORCID logo; Conway, DJORCID logo; Takala-Harrison, S; Plowe, CV; Rayner, JC; Rockett, KA; Clark, TGORCID logo; Newbold, CI; Berriman, M; MacInnis, B; Kwiatkowski, DP and (2012) Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature, 487 (7407). pp. 375-379. ISSN 0028-0836 DOI: 10.1038/nature11174
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Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.


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